Abstract
As NAD(+) is a rate-limiting cosubstrate for the sirtuin enzymes, its modulation is emerging as a valuable tool to regulate sirtuin function and, consequently, oxidative metabolism. In line with this premise, decreased activity of PARP-1 or CD38-both NAD(+) consumers-increases NAD(+) bioavailability, resulting in SIRT1 activation and protection against metabolic disease. Here we evaluated whether similar effects could be achieved by increasing the supply of nicotinamide riboside (NR), a recently described natural NAD(+) precursor with the ability to increase NAD(+) levels, Sir2-dependent gene silencing, and replicative life span in yeast. We show that NR supplementation in mammalian cells and mouse tissues increases NAD(+) levels and activates SIRT1 and SIRT3, culminating in enhanced oxidative metabolism and protection against high-fat diet-induced metabolic abnormalities. Consequently, our results indicate that the natural vitamin NR could be used as a nutritional supplement to ameliorate metabolic and age-related disorders characterized by defective mitochondrial function.
Copyright © 2012 Elsevier Inc. All rights reserved.
Publication types
- Research Support, Non-U.S. Gov't
MeSH terms
- Acetylation
- Adipose Tissue, Brown / drug effects
- Adipose Tissue, Brown / metabolism
- Adipose Tissue, Brown / pathology
- Animals
- Brain / metabolism
- Diet, High-Fat / adverse effects*
- Dietary Supplements
- Electron Transport Complex I / metabolism
- Energy Metabolism
- HEK293 Cells
- Humans
- Liver / metabolism
- Male
- Mice
- Mice, Inbred C57BL
- Mitochondria / metabolism
- Muscle, Skeletal / drug effects
- Muscle, Skeletal / metabolism
- NAD / blood
- NAD / metabolism*
- Niacinamide / administration & dosage
- Niacinamide / analogs & derivatives*
- Niacinamide / pharmacology
- Obesity / etiology
- Obesity / prevention & control*
- Organ Specificity
- Oxidation-Reduction
- Oxygen Consumption
- Protein Processing, Post-Translational
- Pyridinium Compounds
- Receptors, G-Protein-Coupled / metabolism
- Receptors, Nicotinic / metabolism
- Sirtuin 1 / metabolism
- Sirtuin 3 / metabolism
- Superoxide Dismutase / metabolism
- Weight Gain / drug effects
Substances
- HCAR2 protein, human
- Pyridinium Compounds
- Receptors, G-Protein-Coupled
- Receptors, Nicotinic
- nicotinamide-beta-riboside
- NAD
- Niacinamide
- Superoxide Dismutase
- superoxide dismutase 2
- SIRT1 protein, human
- SIRT3 protein, human
- Sirtuin 1
- Sirtuin 3
- Electron Transport Complex I
- NDUFA9 protein, human